African-specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer.
African
genome wide association study
genomics
genotypic ancestry
health disparities
polygenic risk
prostate cancer
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 01 2021
01 01 2021
Historique:
received:
13
05
2020
revised:
07
08
2020
accepted:
12
08
2020
pubmed:
16
9
2020
medline:
11
6
2021
entrez:
15
9
2020
Statut:
ppublish
Résumé
Polygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify single nucleotide polymorphisms (SNPs) that might improve performance in this population. Anonymized genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Ten iterations of a 10-fold cross-validation search were conducted to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African was compared using the same cross-validated approach. Three SNPs (rs76229939, rs74421890 and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47-4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65-0.53). In conclusion, we identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans.
Identifiants
pubmed: 32930425
doi: 10.1002/ijc.33282
pmc: PMC8135907
mid: NIHMS1695898
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
99-105Subventions
Organisme : NIBIB NIH HHS
ID : K08 EB026503
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA182883
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA037429
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA189974
Pays : United States
Informations de copyright
© 2020 Union for International Cancer Control.
Références
BMJ. 2018 Jan 10;360:j5757
pubmed: 29321194
Nat Genet. 2019 Apr;51(4):584-591
pubmed: 30926966
J Natl Cancer Inst. 2016 Jan 27;108(7):
pubmed: 26823525
Nature. 2016 Oct 12;538(7624):161-164
pubmed: 27734877
Clin Epidemiol. 2012;4:1-11
pubmed: 22291478
Nat Genet. 2007 May;39(5):638-44
pubmed: 17401364
Cancer Epidemiol Biomarkers Prev. 2017 Jan;26(1):126-135
pubmed: 27697780
JAMA. 1982 May 14;247(18):2543-6
pubmed: 7069920
BMC Bioinformatics. 2016 Mar 09;17:122
pubmed: 26961892
Cancer Epidemiol Biomarkers Prev. 2020 Sep;29(9):1731-1738
pubmed: 32581112
Cancer Epidemiol Biomarkers Prev. 2008 Aug;17(8):2052-61
pubmed: 18708398
Nat Genet. 2007 May;39(5):645-9
pubmed: 17401363
Nat Commun. 2021 Feb 23;12(1):1236
pubmed: 33623038
Lifetime Data Anal. 1999 Jun;5(2):99-112
pubmed: 10408179
Genome Res. 1999 Aug;9(8):677-9
pubmed: 10447503
Nat Commun. 2019 Jul 25;10(1):3328
pubmed: 31346163